We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
WIKI4, a novel inhibitor of tankyrase and Wnt/ß-catenin signaling.
- Authors
James, Richard G; Davidson, Kathryn C; Bosch, Katherine A; Biechele, Travis L; Robin, Nicholas C; Taylor, Russell J; Major, Michael B; Camp, Nathan D; Fowler, Kerry; Martins, Timothy J; Moon, Randall T
- Abstract
The Wnt/ß-catenin signaling pathway controls important cellular events during development and often contributes to disease when dysregulated. Using high throughput screening we have identified a new small molecule inhibitor of Wnt/ß-catenin signaling, WIKI4. WIKI4 inhibits expression of ß-catenin target genes and cellular responses to Wnt/ß-catenin signaling in cancer cell lines as well as in human embryonic stem cells. Furthermore, we demonstrate that WIKI4 mediates its effects on Wnt/ß-catenin signaling by inhibiting the enzymatic activity of TNKS2, a regulator of AXIN ubiquitylation and degradation. While TNKS has previously been shown to be the target of small molecule inhibitors of Wnt/ß-catenin signaling, WIKI4 is structurally distinct from previously identified TNKS inhibitors.
- Publication
PloS one, 2012, Vol 7, Issue 12, pe50457
- ISSN
1932-6203
- Publication type
Journal Article
- DOI
10.1371/journal.pone.0050457